The primary goal of these studies is to ascertain the role of brain nicotinic receptors in regulating sensitivity to nicotine. Previous studies from our laboratory have demonstrated that inbred mouse strains differ extensively in the development of behavioral and physiological tolerance to nicotine. Chronic administration of nicotine increases the number of brain nicotinic receptors. In a strain of mouse that develops profound tolerance to nicotine, the dose response for receptor up-regulation differs extensively across brain regions. Current studies will determine the relationship between receptor up-regulation and tolerance development in strains of mice that develop little, if any, tolerance to nicotine. These studies may elucidate the neurobiological substrates that are responsible for the expression of tolerance to nicotine. The objective of the collaboration with the Resource is to develop a tool to assist us in rapidly analyzing the large amount of data produced as part of this study. To that end, we are constructing a 3D probability atlas of the mouse brain.